-Complex olfactory-discrimination (OD) learning results in a series of intrinsic and excitatory synaptic modifications in piriform cortex pyramidal neurons that enhance the circuit excitability. Such overexcitation must be balanced to prevent runway activity while maintaining the efficient ability to store memories. We showed previously that OD learning is accompanied by enhancement of the GABA A -mediated inhibition. Here we show that GABA B -mediated inhibition is also enhanced after learning and study the mechanism underlying such enhancement and explore its functional role. We show that presynaptic, GABA B -mediated synaptic inhibition is enhanced after learning. In contrast, the population-average postsynaptic GABA B -mediated synaptic inhibition is unchanged, but its standard deviation is enhanced. Learning-induced reduction in paired pulse facilitation in the glutamatergic synapses interconnecting pyramidal neurons was abolished by application of the GABA B antagonist CGP55845 but not by blocking G proteingated inwardly rectifying potassium channels only, indicating enhanced suppression of excitatory synaptic release via presynaptic GABA B -receptor activation. In addition, the correlation between the strengths of the early (GABA A -mediated) and late (GABA B -mediated) synaptic inhibition was much stronger for each particular neuron after learning. Consequently, GABA B -mediated inhibition was also more efficient in controlling epileptic-like activity induced by blocking GABA A receptors. We suggest that complex OD learning is accompanied by enhancement of the GABA B -mediated inhibition that enables the cortical network to store memories, while preventing uncontrolled activity. olfactory-discrimination learning; piriform cortex; brain slices; synaptic inhibition; GABA B

Once trained, rats are able to execute particularly difficult olfactory discrimination tasks with exceptional accuracy. Such skill acquisition, termed “rule learning”, is accompanied by a series of long‐lasting modifications to three cellular properties which modulate pyramidal neuron activity in piriform cortex; intrinsic excitability, synaptic excitation, and synaptic inhibition. Here, we explore how these changes, which are seemingly contradictory at the single‐cell level in terms of their effect on neuronal excitation, are manifested within the piriform cortical neuronal network to store the memory of the rule, while maintaining network stability. To this end, we monitored network activity via multisite extracellular recordings of field postsynaptic potentials (fPSPS) and with single‐cell recordings of miniature inhibitory and excitatory synaptic events in piriform cortex slices. We show that although 5 days after rule learning the cortical network maintains its basic activity patterns, synaptic connectivity is strengthened specifically between spatially proximal cells. Moreover, while the enhancement of inhibitory and excitatory synaptic connectivity is nearly identical, strengthening of synaptic inhibition is equally distributed between neurons while synaptic excitation is particularly strengthened within a specific subgroup of cells. We suggest that memory for the acquired rule is stored mainly by strengthening excitatory synaptic connection between close pyramidal neurons and runaway synaptic activity arising from this change is prevented by a nonspecific enhancement of synaptic inhibition.

Training rats in a complex olfactory discrimination task results in acquisition of "rule learning" (learning how to learn), a term describing the capability to perform the task superbly. Such rule learning results in strengthening of both excitatory and inhibitory synaptic connections between neurons in the piriform cortex. Moreover, intrinsic excitability is also enhanced throughout the pyramidal neuron population. Surprisingly, the cortical network retains its stability under these long-term modifications. In particular, the susceptibility for long-term potentiation (LTP) induction, while decreased for a short time window, returns to almost its pretraining value, although significant strengthening of AMPA receptor-mediated glutamatergic transmission remains. Such network balance is essential for maintaining the single-cell modifications that underlie long-term memory while preventing hyperexcitability that would result in runaway synaptic activity. However, the mechanisms underlying the long-term maintenance of such balance have yet to be described. In this study, we explored the role of astrocyte-mediated gliotransmission in long-term maintenance of learning-induced modifications in susceptibility for LTP induction and control of the strength of synaptic inhibition. We show that blocking connexin 43 hemichannels, which form gap junctions between astrocytes, decreases significantly the ability to induce LTP by stimulating the excitatory connections between piriform cortex pyramidal neurons after learning only. In parallel, spontaneous miniature inhibitory postsynaptic current amplitude is reduced in neurons from trained rats only, to the level of prelearning. Thus gliotransmission has a key role in maintaining learning-induced cortical stability by a wide-ranged control on synaptic transmission and plasticity. NEW & NOTEWORTHY We explore the role of astrocyte-mediated gliotransmission in maintenance of olfactory discrimination learning-induced modifications. We show that blocking gap junctions between astrocytes decreases significantly the ability to induce long-term potentiation in the piriform cortex after learning only. In parallel, synaptic inhibition is reduced in neurons from trained rats only, to the level of prelearning. Thus gliotransmission has a key role in maintaining learning-induced cortical stability by a wide-ranged control on synaptic transmission and plasticity.

The transmission of heartbeat through the cerebral vascular system is known to cause intracranial pressure pulsations. Here we describe that arterial pressure pulsations within the brain can directly modulate central neuronal activity. In a semi-intact rat brain preparation, pressure pulsations elicit correlated local field oscillations in the olfactory bulb (OB) that are sensitive to hypoxia and block of mechanosensitive channels. We find that mitral cell spiking activity is in part synchronized to these oscillations. Indeed, in awake animals the firing of a subset of OB neurons is entrained to heartbeat within ~ 20 ms. Several lines of evidence indicate the expression of a mechanosensitive ion channel within the mitral cell membranes, most likely Piezo2, implementing a pressure pulsation transduction pathway and thus baroreception within the OB. We propose that this intrinsic interoceptive mechanism modulates OB neuronal activity e.g. during arousal and also could influence brain activity on a wider scale.